Cilostazol combats lipopolysaccharide‐induced hippocampal injury in rats
Role of AKT/GSK3β/CREB curbing neuroinflammation
- verfasst von
- Doaa Abou El-ezz, Waleed Aldahmash, Tuba Esatbeyoglu, Sherif M. Afifi, Marawan Abd Elbaset, Norsharina Ismail
- Abstract
Neuroinflammation is important in the pathophysiology of several degenerative brain disorders. This study looked at the potential neuroprotective benefits of cilostazol, a phosphodiesterase inhibitor, against LPS-induced hippocampus damage in rodents and the principal molecular involvement of AKT/GSK3β/CREB signaling pathways. Behavioral tests revealed that cilostazol successfully corrected LPS-induced neurobehavioral impairments. Furthermore, cilostazol therapy lowered hippocampal levels of amyloid beta 1-42 (Aβ1-42) and p-Tau protein, both of which are critical pathological indicators of neurodegenerative disorders. Furthermore, cilostazol administration suppressed LPS-induced rises in hippocampus caspase-3 and NF-B levels while elevating rat B-cell/lymphoma 2 (BCL2) and brain-derived neurotrophic factor (BDNF) levels, which are implicated in neuronal survival and synaptic plasticity. Cilostazol treatment also restored the decreased phosphorylation of protein kinase B (p-AKT) and reduced the elevated levels of phosphorylated glycogen synthase kinase-3 beta (p-GSK3β) and cAMP response element-binding protein (CREB) in the hippocampus of LPS-Treated rats. Histopathological examination revealed that cilostazol ameliorated LPS-induced brain damage with reduced neuronal loss and gliosis. Immunohistochemistry analysis showed a decrease in Iba-1 expression, indicating a reduction in microglial activation in the cilostazol-Treated group compared to the LPS group. The findings advocate that cilostazol exerts neuroprotective effects against LPS-induced hippocampal injury by modulating the AKT/GSK3β/CREB pathway and curbing neuroinflammation. Cilostazol may hold promise as a therapeutic agent for neuroinflammatory conditions associated with neurodegenerative diseases.
- Organisationseinheit(en)
-
Institut für Lebensmittelwissenschaft und Humanernährung
- Externe Organisation(en)
-
October 6 University
King Saud University
Università di Bologna
National Research Centre (NRC)
- Typ
- Artikel
- Journal
- Advances in Pharmacological and Pharmaceutical Sciences
- Band
- 2024
- Anzahl der Seiten
- 10
- Publikationsdatum
- 26.09.2024
- Publikationsstatus
- Veröffentlicht
- Peer-reviewed
- Ja
- ASJC Scopus Sachgebiete
- Pharmakologie (medizinische), Biochemie, Pharmakologie, Toxikologie und Pharmazie (insg.), Organische Chemie
- Elektronische Version(en)
-
https://doi.org/10.1155/2024/3465757 (Zugang:
Offen)